The use of cell-sheet technique eliminates arrhythmogenicity of skeletal myoblast-based therapy to the heart with enhanced therapeutic effects

Takuya Narita, Yasunori Shintani, Chiho Ikebe, Masahiro Kaneko, Narumi Harada, Nomathamsanqa Tshuma, Kunihiko Takahashi, Niall G. Campbell, Steven R. Coppen, Kenta Yashiro, Yoshiki Sawa, Ken Suzuki

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


Background: Clinical application of skeletal myoblast transplantation has been curtailed due to arrhythmogenicity and inconsistent therapeutic benefits observed in previous studies. However, these issues may be solved by the use of a new cell-delivery mode. It is now possible to generate "cell-sheets" using temperature-responsive dishes without artificial scaffolds. This study aimed to validate the safety and efficacy of epicardial placement of myoblast-sheets (myoblast-sheet therapy) in treating heart failure. Methods and results: After coronary artery ligation in rats, the same numbers of syngeneic myoblasts were transplanted by intramyocardial injection or cell-sheet placement. Continuous radio-telemetry monitoring detected increased ventricular arrhythmias, including ventricular tachycardia, after intramyocardial injection compared to the sham-control, while these were abolished in myoblast-sheet therapy. This effect was conjunct with avoidance of islet-like cell-cluster formation that disrupts electrical conduction, and with prevention of increased arrhythmogenic substrates due to exaggerated inflammation. Persistent ectopic donor cells were found in the lung only after intramyocardial injection, strengthening the improved safety of myoblast-sheet therapy. In addition, myoblast-sheet therapy enhanced cardiac function, corresponding to a 9.2-fold increase in donor cell survival, compared to intramyocardial injection. Both methods achieved reduced infarct size, decreased fibrosis, attenuated cardiomyocyte hypertrophy, and increased neovascular formation, in association with myocardial upregulation of a group of relevant molecules. The pattern of these beneficial changes was similar between two methods, but the degree was more substantial after myoblast-sheet therapy. Conclusion: The cell-sheet technique enhanced safety and therapeutic efficacy of myoblast-based therapy, compared to the current method, thereby paving the way for clinical application.

Original languageEnglish
Pages (from-to)261-269
Number of pages9
JournalInternational Journal of Cardiology
Issue number1
Publication statusPublished - 2013 Sep 20
Externally publishedYes


  • Bioengineering technology
  • Cell-based therapy
  • Cell-sheet technique
  • Heart failure
  • Intramyocardial injection
  • Ventricular arrhythmia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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